MACCS structural keys

SARI is constituted by two individual score components that evaluate the similarity spectrum within a compound class and potency differences between related ligands as the major determinants of SAR characteristics. Two-dimensional structural similarity of compounds is calculated using the Tanimoto coefficient for MACCS structural keys and potency is represented by either pA or pICso values. Both individual scores of the SARI are first calculated in a raw numerical form and then transformed into final normalized scores. 

MACCS structural keys, Symyx Software, San Ramon, CA. 

In addition to the commonly used MACCS structural fragment keys (MDL Information Systems, Inc., San Leandro CA) and Daylight or UNITY fingerprints (Daylight... 

MACCS keys substructure descriptors (0 structural keys)... 

Examples of structural keys are —> Augmented Atoms (AA), atom pairs and related descriptors, and —> atom-type Estate counts. However, the most common structural keys implemented in specific automated tools are MACCS keys, BCI keys, and CACTVS screen vectors [Ihlenfeldt, Takahashi et al, 1994 Voigt, Bienfait et al, 2001]. 

As illustrated in the next section, the use of biological fingerprints, such as from a BioPrint profile, provides a way to characterize, differentiate and cluster compounds that is more relevant in terms ofthe biological activity of the compounds. The data also show that different in silico descriptors based on the chemical structure can produce quite different results. Thus, the selection of the in silico descriptor to be used, which can range from structural fragments (e.g. MACCS keys), through structural motifs (Daylight keys) to pharmacophore/shape keys (based on both the 2D structure via connectivity and from actual 3D conformations), is very important and some form of validation for the problem at hand should be performed. 

Two different MACCS keys (or MDL keys) [MACCS keys - MDL Information Systems Inc., 2008 Durant, Leland et al, 2002] are commonly encountered, one containing 960 bits and the other, which is public, containing a subset of 166 bits (ISIS keys). The fragment dictionary is based on a number of atom types, atom pairs, and custom atom environments. There can be a one-to-one relationship between the structural features and bits, or hashing can be used to create a many-to-one or many-to-many relationship between the features and bits. 

The number of features combined in a vector-type representation is indicative of the dimensionality of the problem space. Low-dimensional representations, on the one hand, allow easy visualization but are most often not very discriminative. Highdimensional representations, on the other hand, such as those encoded in Daylight fingerprints [23], MACCS keys [24], or UNITY fingerprints [25], provide more detailed accounts on structural or chemical variations. However, this is achieved at the cost of visualization. Part of these high-dimensional representations describe specific local features of molecules, and because not all molecules in the data contain these features, gaps or zeros are introduced in the data representation. For certain data mining methods, this could be problematic. In many cases, dimensionality reduction procedures are applied to reduce the complexity of the representation. The reduction of the dimensionality is accomplished by means of 1) variable selection procedures, 2)... 

Tanimoto coefficients between the seven hit structures and the most similar analogues were calculated on the basis of MACCS keys and graph-3-point pharmacophore fingerprints. The actual docking rank from the docking of the 320 Maybridge compounds that passed the pharmacophore model is indicated. 

Two key features incorporated into ChemSketch allow the creation of composite documents. The first is the MACCS interface. The user, after extracting an MDL metafile can press the M keyboard switch and quickly review or modify the structure or reaction on the screen. The second key feature is the Save for DECpage command. This command converts the currently displayed structure into a file which contains the ReGIS commands required by DECpage to produce the composite document. Figure 4a is an example of a structure that was extracted from the Fine Chemicals Database of MACCS and placed into this document. 

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